Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) (ATTACC)

Inclusion Criteria:

1. Patients ≥18 years of age providing (possibly through a substitute decision maker) informed consent who require hospitalization anticipated to last ≥72 hours, for microbiologically-confirmed COVID-19, enrolled < 72 hours of hospital admission or of COVID-19 confirmation

• If the patient is already hospitalized and the COVID-19 diagnosis is due to an outbreak or an incidental finding, then enrollment can occur within 72 hours of a clinical syndrome attributable to COVID-19 that requires continued hospitalization (e.g. new or worsening oxygen requirements or acute kidney injury) which is further anticipated to extend the hospital admission by an additional 72 hours from randomization.

Exclusion Criteria:

1. Patients admitted to an ICU AND receiving organ support (i.e. high flow nasal oxygen, receiving non-invasive or invasive mechanical ventilation, or are requiring vasopressor/inotrope)
2. Patients for whom the intent is to not use pharmacologic thromboprophylaxis
3. Active bleeding

4. Risk factors for bleeding, including:

   1. intracranial surgery or stroke within 3 months;
   2. history of intracerebral arteriovenous malformation;
   3. cerebral aneurysm or mass lesions of the central nervous system;
   4. intracranial malignancy
   5. history of intracranial bleeding
   6. history of bleeding diatheses (e.g., hemophilia)
   7. history of gastrointestinal bleeding within previous 3 months
   8. thrombolysis within the previous 7 days
   9. presence of an epidural or spinal catheter
   10. recent major surgery <14 days
   11. uncontrolled hypertension (sBP >200 mmHg, dBP >120 mmHg)
   12. other physician-perceived contraindications to anticoagulation
5. Platelet count <50 x10^9/L, INR >2.0, or baseline aPTT >50 (if available per SOC testing)
6. Hemoglobin <80 g/L (to minimize the likelihood of requiring red blood cell transfusion if potential bleeding were to occur)
7. Acute or subacute bacterial endocarditis
8. History of heparin induced thrombocytopenia (HIT) or other heparin allergy including hypersensitivity
9. Current use of dual antiplatelet therapy
10. Patients with an independent indication for therapeutic anticoagulation
11. Patients in whom imminent demise is anticipated and there is no commitment to active ongoing intervention
12. Anticipated transfer to another hospital that is not a study site within 72 hours
13. Enrollment in other trials related to anticoagulation or antiplatelet therapy